In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs

• Published in: European journal of medicinal chemistry Vol. 145; pp. 735 - 745
• Main Authors: Yadav, Neesha, Agarwal, Drishti, Kumar, Satyanand, Dixit, A.K., Gupta, Rinkoo D., Awasthi, Satish K.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 10.02.2018; Elsevier
• Subjects: Antiplasmodial; Chemistry, Medicinal; Coumarin; DNA gyrase; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plasmodium falciparum; Science & Technology; Plasmodium falciparum; Antiplasmodial; Coumarin; DNA gyrase; ANTIMALARIAL ACTIVITY; AGENTS; CHALCONE; DERIVATIVES
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.01.017

Twenty two diverse coumarin-triazole derivatives were synthesized by alkylation of 7-hydroxy-4-methyl-coumarin followed by click chemistry at 7-position. These compounds were evaluated for their in vitro antiplasmodial activity against chloroquine sensitive strain of Plasmodium falciparum (3D7). Compound 9 (7-[1-(2, 4-dimethoxy-phenyl)-1H- [1–3] triazol-4-ylmethoxy]-4-methyl-chromen-2-one) was found most active with IC50 value 0.763 ± 0.0124 μg/mL. Further, the structure of compound 20 was characterized by single crystal X-ray diffraction. In view of impressive results, we considered it worthwhile to validate the results of in vitro antiplasmodial activity by assessing whether these compounds are capable of hampering the catalytic activity of DNA gyrase, thus preventing its supercoiling function. [Display omitted] •Coumarin-triazole derivatives were synthesized by alkylation of 7-hydroxy-4-methyl-coumarin followed by click chemistry.•Most of the compounds demonstrated promising in vitro antiplasmodial activities.•They displayed inhibition of the supercoiling activity of DNA gyrase enzyme.